Similar Datasets
Project description:RNA sequencing (RNAseq) of SCC9 cells transduced with TEAD inhibitor protein (TEADi) or control GFP
2021-07-01 | GSE156912 | GEO
Project description:TEAD inhibition in human keratinocytes
| PRJNA563904 | ENA
Project description:RNA sequencing (RNAseq) of primary keratinocytes from mouse basal cell carcinoma mice (BCC) transduced with pooled siRNAs targeting YAP1 and TAZ (siYT) or non-targeting control siRNA (siCon), and with TEADi or GFP as control
2021-06-09 | GSE156913 | GEO
Project description:RNA sequencing (RNAseq) of N/TERT2G keratinocytes transduced with pooled siRNAs targeting KLF4, or non-targeting control siRNA (siCon)
2020-02-24 | GSE137410 | GEO
Project description:RNA sequencing (RNAseq) of N/TERT2G keratinocytes transduced with pooled siRNAs targeting YAP1 and TAZ (WWTR1), or non-targeting control siRNA (siCon)
2020-02-24 | GSE137531 | GEO
Project description:RNA sequencing (RNAseq) of primary neonatal human keratinocytes transduced with pooled siRNAs targeting LTB4R, HCAR3, GPR153, and GPR137, or non-targeting control siRNA (siCon)
2023-07-21 | GSE228651 | GEO
Project description:TEAD transcription factors (TEAD1-4) serve as the primary effectors of the Hippo signaling pathway in various cancers. There has been significant progress in the development of therapeutic strategies aimed at disrupting the interaction of TEAD with its coactivators YAP/TAZ. However, targeted therapy leads to the emergence of resistance which poses a barrier to achieving complete cures. Currently, the underlying mechanism of resistance to TEAD inhibition in cancers remains unexplored. We uncover that upregulation of the AP-1 transcription factors, along with restored YAP/TEAD activity, drives resistance to GNE-7883, a pan-TEAD and allosteric TEAD inhibitor. Acute GNE-7883 treatment abrogates YAP binding and attenuates FOSL1 activity but compensation by increased MAPK pathway activity remains insufficient for cell survival. In contrast, TEAD inhibitor resistant cells are able to restore YAP and TEAD occupancy and acquire additional FOSL1 binding sites, leading to increased chromatin accessibility at AP-1 motifs. Resistant cells undergo transcriptional reprogramming to acquire a mesenchymal-like cell state and sustained MAPK activity. We uncover a dependence on the MAPK pathway in the TEAD inhibitor resistant cells, further highlighting the key role of MAPK pathway inhibitors, such as Cobimetinib and Belvarafenib to mitigate resistance mechanisms to TEAD inhibition in Hippo pathway dependent cancers. This study describes a clinically relevant interplay between the Hippo and MAPK pathway in cancers and offers a promising avenue to address TEAD inhibitor resistance in the clinic.
2024-12-17 | GSE273358 | GEO
Project description:Objectives: To define the inflammatory signature of healthy keratinocytes induced by gram-negative anaerobe bacteria commonly found in HS and investigate pathways of activation. Methods: Type strains of P. nigrescens, P. melanogenica, P. intermedia, P. asaccharolytica, F. nucleatum, as well as S. aureus and the normal skin commensal S. epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was analyzed using RNAseq and RT-qPCR. TLR4 and JAK inhibitors were used to investigate mRNA and protein inhibition of inflammatory cytokines. Results: All GNAs tested induced significantly higher levels of CXCL8 than S. epidermidis or negative control. P. nigrescens, P. melanogenica, and F. nucleatum were the most stimulatory and produced CXCL8 levels much higher than S. aureus. RNASeq revealed a broad inflammatory profile most strongly induced by F. nucleatum. All three bacteria strongly activated the IL-17 pathway and correlated with HS skin transcriptomes. Both TLR4 and JAK inhibition significantly reduced keratinocyte inflammation. Results: All GNAs tested induced significantly higher levels of CXCL8 than S. epidermidis or negative control. P. nigrescens, P. melanogenica, and F. nucleatum were the most stimulatory and produced CXCL8 levels much higher than S. aureus. RNASeq revealed a broad inflammatory profile most strongly induced by F. nucleatum. All three bacteria strongly activated the IL-17 pathway and correlated with HS skin transcriptomes.
2024-06-30 | GSE237052 | GEO
Project description:We have compared the response to TGFbeta1 in normal and v-rasHa transduced primary mouse keratinocytes using NCI cDNA microarrays. This analysis reveals that Ha-ras alters global TGFbeta1 mediated gene expression in a gene specific manner. The expression pattern of TGFbeta1 immediate early response genes and down regulation of cell cycle control genes is not altered by Ha-ras but the induction of most extracellular matrix genes is blocked. Using Smad3 null keratinocytes, we find that the majority of TGFbeta1 responsive genes in primary keratinocytes are Smad3 dependent, but patterns of transcriptional responses suggest that the ability of Ha-ras to block TGFbeta1 mediated gene expression is not dependent on Smad3. However, the combination of oncogenic ras and loss of Smad3 prevents the TGFbeta1 dependent suppression of genes associated with cell cycle progression and apoptosis observed with either genotype alone. In addition several extracellular matrix genes are super-repressed by TGFbeta1 in the Ha-ras Smad3 null keratinocytes. These data provide a genomic framework for understanding how disruptions of TGFbeta signaling and oncogenic ras cooperate to promote premalignant progression of primary keratinocytes. Keywords: time series design RNA from Balb/c primary and ras keratinocytes treated for 1, 6, 24, and 48 hours with TGFbeta1 at 1ng/ml was compared to RNA from the corresponding untreated controls. For each timepoint sample from primary and ras cells, multiple arrays (including dye swaps) were analyzed. There are 6, 7, 6, and 5 arrays analyzed for RNA from primary keratinocytes treated for 1, 6, 24, and 48 hours as compared to RNA from untreated primary cells, respectively. There are 6, 8, 7, and 5 arrays analyzed for RNA from ras keratinocytes treated for 1, 6, 24, and 48 hours as compared to RNA from untreated ras cells, respectively. There are 50 arrays analyzed for the Balb/c time-course dataset. RNA from Smad3 WT and KO primary and ras keratinocytes treated 48 hours with TGFbeta1 were compared to RNA from its untreated corresponding controls. There are 6 arrays analyzed for the Smad3 WT/KO data set. There are 56 arrays in this series.
2010-06-30 | E-GEOD-3228 | biostudies-arrayexpress